Fibrosing Cholestatic Hepatitis C and Viral Clearance in the Post Transplant Setting

Abstract

Purpose: Hepatitis C (HCV) is the leading indication for liver transplantation (OLT). HCV recurrence after OLT is universal. Fibrosing cholestatic HCV (FCH) is a severe form of HCV characterized by high viral loads, transaminitis & hyperbilirubinemia. Methods: We describe 3 cases that underwent OLT for HCV. After immunosuppression was minimized, all 3 developed severe transaminitis with jaundice as well as loss of circulating HCV. Results: Case 1: 15 months after OLT, 53-yr-old male developed acute rise in LFTs (AST 295; ALT 209; ALP-734; T. Bili 1.8) with HCV RNA > 7 log IU/cc). Liver biopsy (Bx) was consistent with FCH. Antiviral therapy was started with PEG-Interferon (IFN) and Ribavirin (RBV). Complete viral clearance was noted. Despite viral clearance, the patient succumbed to hepatic decompensation. Case2: Three months after OLT, 44-yr-old male developed recurrent HCV with elevated LFTs and was started on IFN and RBV which was discontinued at 6 months due to depression. 12 months later, he was placed on Infergen. 22 months into therapy, an acute, severe transaminitis with jaundice was noted (ALT-252; AST-452; T. Bili-7.2). Bx showed interface hepatitis and canalicular cholestasis consistent with overlap features of rejection and FCH. A repeat HCV RNA was undetectable at < 550 IU/ml. 5 years later, his HCV RNA is undetectable. Case 3: 47-yr-old female with HCV and hepatocellular carcinoma underwent OLT. At 24-months post OLT, she developed a minimal transaminitis; bx was consistent with recurrent HCV. Immunosuppression was lowered and she subsequently developed major transaminitis associated with jaundice (ALT-1095; AST-1320; ALP-298; T. Bili-13.5). Bx showed interface hepatitis and fibrosis compatible with FCH. Immunosuppression was further lowered. A repeat HCV PCR was negative and viral load was undetectable. Antiviral therapy was not initiated due to spontaneous viral clearance. Despite viral clearance, she developed decompensated liver disease from advanced fibrosis and succumbed to her condition while awaiting re-transplant. Conclusion: FCH is an uncommon but well described entity in immunosuppressed patients with HCV. A high index of suspicion and expert pathology review when encountered with cholestatic labs and high viral loads in post transplant patients is key to the early diagnosis and management of this serious yet potentially reversible condition. The unifying feature of these three patients is that all cleared HCV after a marked transaminitis when immunosuppression was lowered. This may indicate a robust immune response leading to viral clearance similar to what is seen in cases of acute Hepatitis B.